Facilitating Organizational Adoption of Sensor-Based Systems: Espoused Beliefs, Shared Assumptions and Perceived Values

The advent of sensor-based systems with their ability to collect, transmit and process context-aware data creates new opportunities for service delivery. We know from earlier research that there may be barriers to the adoption of new information technology (IT) within an organization. Sensor-based systems, with unprecedented potential for monitoring of products, people and processes are an interesting mix of potential and risk. Through the lens of organizational culture theory, we examine the question: Given the ambiguity and complexity of sensor-based systems, how does organizational culture influence perceptions of system value and purpose, and which factors determine the susceptibility of adoption among individual workers and teams? Our results suggest that the adoption of sensor-based systems is facilitated by 1) a basic comprehension of the system, its functionality, purpose and limitations; 2) a shared view of stakeholders’ roles and responsibilities, and 3) a pronounced and tangible vision for value creation

Uncovering Indicators of the International Classification of Functioning, Disability, and Health from the 39-Item Parkinson's Disease Questionnaire

The 39-item Parkinson's disease questionnaire (PDQ-39) is the most widely used patient-reported rating scale in Parkinson's disease (PD). However, recent studies have questioned its validity and it is unclear what scores represent. This study explored the possibility of regrouping PDQ-39 items into scales representing the International Classification of Functioning, Disability, and Health (ICF) components of Body Functions and Structures (BF), Activities and Participation (AP), and Environmental (E) factors. An iterative process using Rasch analysis produced five new items sets, two each for the BF and AP components and one representing E. Four of these were found to represent clinically meaningful variables: Emotional Impairment (BF), Gross Motor Disability (AP), Fine Motor Disability (AP), and Socioattitudinal Environment (E) with acceptable reliability (0.73–0.96) and fit to the Rasch model (total item-trait chi-square, 8.28–33.2; P > .05). These new ICF-based scales offer a means to reanalyze PDQ-39 data from an ICF perspective and to study its health components using a widely available health status questionnaire for people with PD

Change Agents and Resilient Practices: The Power of Symbolic Capital in a Post-Merger Integration Context

This study analyzes the interactions among mandated change agents within a post-merger integration context and examines the implications of their practices as they attempt to engage with others in a cross-boundary information system implementation project. We examine the case of the Metropolitan Healthcare Center, where three previously independent centers were merged into one, and follow the individuals who were appointed to ensure the integration of a new, mutual information system across the three center sites. We draw on a practice perspective and the notion of symbolic capital to shed light on post-merger practices and their outcomes. Our analysis suggests that one of the change agent’s practices of boundary consolidation through influence tactics were legitimized through discourses of authoritative knowledge and ‘group-making’. This facilitated the construction of symbolic boundaries between the merging parties, thus contributing to the resilience of pre-merger practices despite the planned intention to create change

Altered fibroblast proteoglycan production in COPD

<p>Abstract</p> <p>Background</p> <p>Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production.</p> <p>Methods</p> <p>Proliferation, proteoglycan production and the response to TGF-β₁were examined <it>in vitro </it>in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV) and from control subjects.</p> <p>Results</p> <p>Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma. Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p < 0.01). In addition, perlecan production was lower in centrally derived fibroblasts from COPD patients than from control subjects (p < 0.01). TGF-β₁triggered similar increases in proteoglycan production in distally derived fibroblasts from COPD patients and control subjects. In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-β₁than those from control subjects.</p> <p>Conclusions</p> <p>The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development. Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil. In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD.</p

Effect of the integration method on the accuracy and computational efficiency of free energy calculations using thermodynamic integration

Although calculations of free energy using molecular dynamics simulations have gained significant importance in the chemical and biochemical fields, they still remain quite computationally intensive. Furthermore, when using thermodynamic integration, numerical evaluation of the integral of the Hamiltonian with respect to the coupling parameter may introduce unwanted errors in the free energy. In this paper, we compare the performance of two numerical integration techniques-the trapezoidal and Simpson's rules and propose a new method, based on the analytic integration of physically based fitting functions that are able to accurately describe the behavior of the data. We develop and test our methodology by performing detailed studies on two prototype systems, hydrated methane and hydrated methanol, and treat Lennard-Jones and electrostatic contributions separately. We conclude that the widely used trapezoidal rule may introduce systematic errors in the calculation, but these errors are reduced if Simpson's rule is employed, at least for the electrostatic component. Furthermore, by fitting thermodynamic integration data, we are able to obtain precise free energy estimates using significantly fewer data points (5 intermediate states for the electrostatic component and 11 for the Lennard-Jones term), thus significantly decreasing the associated computational cost. Our method and improved protocol were successfully validated by computing the free energy of more complex systems hydration of 2-methylbutanol and of 4-nitrophenol-thus paving the way for widespread use in solvation free energy calculations of drug molecules

The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5 epimerization of glucuronic acid in higher organisms

Dermatan sulfate epimerase 1 DS epi1, EC 5.1.3.19 catalyzes the conversion of D glucuronic acid to L iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS epi1, solved at 2.4 resolution, as well as a model of the full length luminal protein obtained by a combination of macromolecular crystallography and targeted cross linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS epi1, involving a His double Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal coordinating center and pattern of N glycosylation of the protein. Additionally, the structure of DS epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitor

Functional and phenotypical comparison of myofibroblasts derived from biopsies and bronchoalveolar lavage in mild asthma and scleroderma

BACKGROUND: Activated fibroblasts, which have previously been obtained from bronchoalveolar lavage fluid (BALF), are proposed to be important cells in the fibrotic processes of asthma and scleroderma (SSc). We have studied the motility for BALF derived fibroblasts in patients with SSc that may explain the presence of these cells in the airway lumen. Furthermore, we have compared phenotypic alterations in activated fibroblasts from BALF and bronchial biopsies from patients with mild asthma and SSc that may account for the distinct fibrotic responses. METHODS: Fibroblasts were cultured from BALF and bronchial biopsies from patients with mild asthma and SSc. The motility was studied using a cell migration assay. Western Blotting was used to study the expression of alpha-smooth muscle actin (α-SMA), ED-A fibronectin, and serine arginine splicing factor 20 (SRp20). The protein expression pattern was analyzed to reveal potential biomarkers using two-dimensional electrophoresis (2-DE) and sequencing dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF). The Mann-Whitney method was used to calculate statistical significance. RESULTS: Increased migration and levels of ED-A fibronectin were observed in BALF fibroblasts from both groups of patients, supported by increased expression of RhoA, Rac1, and the splicing factor SRp20. However, these observations were exclusively accompanied by increased expression of α-SMA in patients with mild asthma. Compared to BALF fibroblasts in mild asthma, fibroblasts in SSc displayed a differential protein expression pattern of cytoskeletal- and scavenger proteins. These identified proteins facilitate cell migration, oxidative stress, and the excessive deposition of extracellular matrix observed in patients with SSc. CONCLUSION: This study demonstrates a possible origin for fibroblasts in the airway lumen in patients with SSc and important differences between fibroblast phenotypes in mild asthma and SSc. The findings may explain the distinct fibrotic processes and highlight the motile BALF fibroblast as a potential target cell in these disorders

Global guidelines for the sustainable use of non-native trees to prevent tree invasions and mitigate their negative impacts

Sustainably managed non-native trees deliver economic and societal benefits with limited risk of spread to adjoining areas. However, some plantations have launched invasions that cause substantial damage to biodiversity and ecosystem services, while others pose substantial threats of causing such impacts. The challenge is to maximise the benefits of non-native trees, while minimising negative impacts and preserving future benefits and options. A workshop was held in 2019 to develop global guidelines for the sustainable use of non-native trees, using the Council of Europe – Bern Convention Code of Conduct on Invasive Alien Trees as a starting point. The global guidelines consist of eight recommendations: 1) Use native trees, or non-invasive non-native trees, in preference to invasive non-native trees; 2) Be aware of and comply with international, national, and regional regulations concerning non-native trees; 3) Be aware of the risk of invasion and consider global change trends; 4) Design and adopt tailored practices for plantation site selection and silvicultural management; 5) Promote and implement early detection and rapid response programmes; 6) Design and adopt tailored practices for invasive non-native tree control, habitat restoration, and for dealing with highly modified ecosystems; 7) Engage with stakeholders on the risks posed by invasive non-native trees, the impacts caused, and the options for management; and 8) Develop and support global networks, collaborative research, and information sharing on native and non-native trees. The global guidelines are a first step towards building global consensus on the precautions that should be taken when introducing and planting non-native trees. They are voluntary and are intended to complement statutory requirements under international and national legislation. The application of the global guidelines and the achievement of their goals will help to conserve forest biodiversity, ensure sustainable forestry, and contribute to the achievement of several Sustainable Development Goals of the United Nations linked with forest biodiversity

Simvastatin inhibits TGFβ1-induced fibronectin in human airway fibroblasts

<p>Abstract</p> <p>Background</p> <p>Bronchial fibroblasts contribute to airway remodelling, including airway wall fibrosis. Transforming growth factor (TGF)-β1 plays a major role in this process. We previously revealed the importance of the mevalonate cascade in the fibrotic response of human airway smooth muscle cells. We now investigate mevalonate cascade-associated signaling in TGFβ1-induced fibronectin expression by bronchial fibroblasts from non-asthmatic and asthmatic subjects.</p> <p>Methods</p> <p>We used simvastatin (1-15 μM) to inhibit 3-hydroxy-3-methlyglutaryl-coenzyme A (HMG-CoA) reductase which converts HMG-CoA to mevalonate. Selective inhibitors of geranylgeranyl transferase-1 (GGT1; GGTI-286, 10 μM) and farnesyl transferase (FT; FTI-277, 10 μM) were used to determine whether GGT1 and FT contribute to TGFβ1-induced fibronectin expression. In addition, we studied the effects of co-incubation with simvastatin and mevalonate (1 mM), geranylgeranylpyrophosphate (30 μM) or farnesylpyrophosphate (30 μM).</p> <p>Results</p> <p>Immunoblotting revealed concentration-dependent simvastatin inhibition of TGFβ1 (2.5 ng/ml, 48 h)-induced fibronectin. This was prevented by exogenous mevalonate, or isoprenoids (geranylgeranylpyrophosphate or farnesylpyrophosphate). The effects of simvastatin were mimicked by GGTI-286, but not FTI-277, suggesting fundamental involvement of GGT1 in TGFβ1-induced signaling. Asthmatic fibroblasts exhibited greater TGFβ1-induced fibronectin expression compared to non-asthmatic cells; this enhanced response was effectively reduced by simvastatin.</p> <p>Conclusions</p> <p>We conclude that TGFβ1-induced fibronectin expression in airway fibroblasts relies on activity of GGT1 and availability of isoprenoids. Our results suggest that targeting regulators of isoprenoid-dependent signaling holds promise for treating airway wall fibrosis.</p